Cellular Metabolism and Induced Pluripotency

Wu, Jun; Ocampo, Alejandro; Belmonte, Juan Carlos Izpisúa

doi:10.1016/j.cell.2016.08.008

Cited by 140 publications

(118 citation statements)

References 115 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…In addition to changes in mitochondrial morphology, cell reprogramming induces a metabolic switch: from an oxidative-somatic state to a glycolytic-pluripotent state [153]. This metabolic remodeling presents several similarities with the Warburg effect observed in cancer cells [154].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Dynamics: In Cell Reprogramming as It Is in Cancer

Prieto

Torres

2017

Stem Cells International

View full text Add to dashboard Cite

Somatic cells can be reprogrammed into a pluripotent cellular state similar to that of embryonic stem cells. Given the significant physiological differences between the somatic and pluripotent cells, cell reprogramming is associated with a profound reorganization of the somatic phenotype at all levels. The remodeling of mitochondrial morphology is one of these dramatic changes that somatic cells have to undertake during cell reprogramming. Somatic cells transform their tubular and interconnected mitochondrial network to the fragmented and isolated organelles found in pluripotent stem cells early during cell reprogramming. Accordingly, mitochondrial fission, the process whereby the mitochondria divide, plays an important role in the cell reprogramming process. Here, we present an overview of the importance of mitochondrial fission in both cell reprogramming and cellular transformation.

show abstract

Section: Discussionmentioning

confidence: 99%

Mitochondrial Dynamics: In Cell Reprogramming as It Is in Cancer

Prieto

Torres

2017

Stem Cells International

View full text Add to dashboard Cite

show abstract

“…Early events in stem cell differentiation occur rapidly, and thus changes in metabolism as a driver of such events is an attractive hypothesis 40 . Indeed the influence of metabolism in the maintenance of stem cell pluripotency has been extensively explored 5, 40, 70–74 . The effects of metabolism on stem cell fate have been recently reviewed in detail elsewhere 3, 5, 75 and thus here we will touch on specific aspects that highlight their interplay.…”

Section: Introductionmentioning

confidence: 99%

“…Two subsets of embryonic stem cells (ESCs), termed naïve and primed, have been defined based on their distinct pluripotency versus differentiation properties, and are also characterized by epigenetically distinct states 5, 40 . Naïve pluripotent stem cells are characterized by their ability to form all cell types without bias, whereas primed pluripotent stem cells are considered to be poised for lineage differentiation 5, 40 .…”

Section: Introductionmentioning

confidence: 99%

“…Naïve pluripotent stem cells are characterized by their ability to form all cell types without bias, whereas primed pluripotent stem cells are considered to be poised for lineage differentiation 5, 40 . In general, high rates of glycolysis even in the presence of oxygen, a phenomenon known as the Warburg Effect 28 , is prevalent in pluripotency and appears to be dynamically regulated in order to facilitate the differentiation process 76 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The impact of cellular metabolism on chromatin dynamics and epigenetics

2017

View full text Add to dashboard Cite

The substrates used to modify nucleic acids and chromatin are affected by nutrient availability and the activity of metabolic pathways. Thus, cellular metabolism constitutes a fundamental component of chromatin status and thereby of genome regulation. Here we describe the biochemical and genetic principles of how metabolism can influence chromatin biology and epigenetics, discuss the functional roles of this interplay in developmental and cancer biology, and present future directions in this rapidly emerging area.

show abstract

“…Recently an adaptive, process-dependent flexibility of the hPSC metabolism at the pluripotent state was reported 21 , and metabolic changes ( i.e . glycolysis vs. oxidative phosphorylation) during hPSC differentiation and somatic cell reprograming into hiPSC are well established 64, 65 . The known inhibitory role of insulin, for example, during cardiac mesoderm induction of hPSCs 66, 67 and the effects on viability at the pluripotent state shown in this study strongly mandate process-dependent adaptation and monitoring of the insulin concentration in the future.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity of human pluripotent stem cells to insulin precipitation induced by peristaltic pump-based medium circulation: considerations on process development

Massai

Bolesani

Diaz

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Controlled large-scale production of human pluripotent stem cells (hPSCs) is indispensable for their envisioned clinical translation. Aiming at advanced process development in suspension culture, the sensitivity of hPSC media to continuous peristaltic pump-based circulation, a well-established technology extensively used in hydraulically-driven bioreactors, was investigated. Unexpectedly, conditioning of low protein media (i.e. E8 and TeSR-E8) in a peristaltic pump circuit induced severe viability loss of hPSCs cultured as aggregates in suspension. Optical, biochemical, and cytological analyses of the media revealed that the applied circulation mode resulted in the reduction of the growth hormone insulin by precipitation of micro-sized particles. Notably, in contrast to insulin depletion, individual withdrawal of other medium protein components (i.e. bFGF, TGFβ1 or transferrin) provoked minor reduction of hPSC viability, if any. Supplementation of the surfactant glycerol or the use of the insulin analogue Aspart did not overcome the issue of insulin precipitation. In contrast, the presence of bovine or human serum albumin (BSA or HSA, respectively) stabilized insulin rescuing its content, possibly by acting as molecular chaperone-like protein, ultimately supporting hPSC maintenance. This study highlights the potential and the requirement of media optimization for automated hPSC processing and has broad implications on media development and bioreactor-based technologies.

show abstract

Cellular Metabolism and Induced Pluripotency

Cited by 140 publications

References 115 publications

Mitochondrial Dynamics: In Cell Reprogramming as It Is in Cancer

Mitochondrial Dynamics: In Cell Reprogramming as It Is in Cancer

The impact of cellular metabolism on chromatin dynamics and epigenetics

Sensitivity of human pluripotent stem cells to insulin precipitation induced by peristaltic pump-based medium circulation: considerations on process development

Contact Info

Product

Resources

About